Submissions for variant NM_000038.6(APC):c.3624C>T (p.Thr1208=)

gnomAD frequency: 0.00007  dbSNP: rs730882125

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV004562332	SCV000211906	likely benign	Familial adenomatous polyposis 1	2025-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000163381	SCV000213921	likely benign	Hereditary cancer-predisposing syndrome	2014-06-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV000679057	SCV000512071	likely benign	not provided	2020-03-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163381	SCV000681618	likely benign	Hereditary cancer-predisposing syndrome	2016-11-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000679057	SCV000805400	likely benign	not provided	2016-11-22	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000679057	SCV001133326	benign	not provided	2019-06-06	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000440935	SCV001361160	benign	not specified	2019-09-12	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163381	SCV002533847	likely benign	Hereditary cancer-predisposing syndrome	2022-01-12	criteria provided, single submitter	curation
All of Us Research Program, National Institutes of Health	RCV003998533	SCV004837813	likely benign	Classic or attenuated familial adenomatous polyposis	2023-12-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004562332	SCV004932021	benign	Familial adenomatous polyposis 1	2024-03-21	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000440935	SCV005090695	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000679057	SCV005226891	likely benign	not provided		criteria provided, single submitter	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353704	SCV000591149	likely benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The APC p.Thr1208Thr variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site; in addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified in the Exome Aggregation Consortium (ExAC) database in 23 of 66362 chromosomes from a population of European (non-Finnish) individuals (frequency: 0.0003), and in the the ClinVar database where it was classified as a likely benign variant by two submitters (Invitae and Ambry Genetics). The variant was not identified in the literature, nor was it identified in any other databases searched. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign.
Clinical Genetics, Academic Medical Center	RCV000679057	SCV001922484	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000679057	SCV001957342	likely benign	not provided		no assertion criteria provided	clinical testing